Role of the Clp system in stress tolerance, Biofilm formation, and intracellular invasion in Porphyromonas gingivalis
Role of the Clp system in stress tolerance, Biofilm formation, and intracellular invasion in Porphyromonas gingivalis
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DOI：
10.1128/jb.01632-07
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发表时间：
2008-02-01
影响因子：
3.2
通讯作者：
Lamont, Richard J.
中科院分区：
文献类型：
--
作者：
Capestany, Cindy A.;Tribble, Gena D.;Lamont, Richard J.
Clp蛋白酶和伴侣蛋白在原核生物和真核生物中普遍存在，在许多致病菌中，Clp应激反应系统也参与毒力特性的调节。本研究探讨了ClpB、ClpC和ClpXP在口腔条件致病菌牙龈卟啉单胞菌的抗逆性、同型和异型生物膜形成以及细胞内侵袭中的作用。不含ClpC和ClpXP，但不含ClpB，导致耐高温能力下降。对氧化应激的反应不受任何Clp蛋白损失的影响。clpC和clpXP突变体表现出单种生物膜形成的增加，而clpXP的缺失也增强了异型牙龈卟啉链球菌-戈登链球菌生物膜的形成。所有clp突变体对牙龈上皮细胞的粘附程度与野生型相同；然而，ClpC和ClpXP被发现是进入宿主上皮细胞所必需的。CIpB在进入过程中不起作用，但却是细胞内复制和存活所必需的。ClpXP负向调节牙龈假单胞菌小毛膜（Mfa）蛋白亚基的表面暴露，刺激生物膜的形成，但干扰上皮细胞的进入。总之，这些结果表明Clp蛋白酶复合物和伴侣控制着牙龈卟啉卟啉菌在口腔内定植和存活的几个重要过程。
Clp proteases and chaperones are ubiquitous among prokaryotes and eukaryotes, and in many pathogenic bacteria the Clp stress response system is also involved in regulation of virulence properties. In this study, the roles of ClpB, ClpC, and ClpXP in stress resistance, homotypic and heterotypic biofilm formation, and intracellular invasion in the oral opportunistic pathogen Porphyromonas gingivalis were investigated. Absence of ClpC and ClpXP, but not ClpB, resulted in diminished tolerance to high temperatures. Response to oxidative stress was not affected by the loss of any of the Clp proteins. The clpC and clpXP mutants demonstrated elevated monospecies biofilm formation, and the absence of ClpXP also enhanced heterotypic P. gingivalis-Streptococcus gordonii biofilm formation. All clp mutants adhered to gingival epithelial cells to the same level as the wild type; however, ClpC and ClpXP were found to be necessary for entry into host epithelial cells. CIpB did not play a role in entry but was required for intracellular replication and survival. ClpXP negatively regulated the surface exposure of the minor fimbrial (Mfa) protein subunit of P. gingivalis, which stimulates biofilm formation but interferes with epithelial cell entry. Collectively, these results show that the Clp protease complex and chaperones control several processes that are important for the colonization and survival of P. gingivalis in the oral cavity.